Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
  • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
  • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
  • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
  • C07H19/06—Pyrimidine radicals

Definitions

• This invention relates to certain deoxyuridine compounds which have antiviral activity.
• UK Patent Specification No. 1601020 discloses 5-(2-halogenovinyl)-2'-deoxyuridines which have antiviral activity selective against herpes virus.
• the derivatives give surprisingly prolonged high levels of antiviral activity in the blood of animals when administered orally.
• the compounds of formula (I) may be prepared by treating a 5-(2-halogenovinyl)-2'-deoxyuridine compound of formula (II): in which Y is as defined in formula (I) with a methyl halide of formula CH 3 X, in which X is a halogen atom, preferably an iodine atom.
• the reaction is suitably carried out in a polar organic solvent, preferably anhydrous tetrahydrofuran, at room temperature, and is preferably catalysed by fluoride ions.
• a polar organic solvent preferably anhydrous tetrahydrofuran
• the product is preferably purified chromatographically by, for example, column chromatography on silica gel.
• An alternative process for preparing the compounds of formula (I) comprises treating a compound of formula (II) as defined above with N,N-dimethyl formamide dimethylacetal, preferably in the presence of an acid catalyst such as trifluoroacetic acid.
• the process is suitably carried out under an inert atmosphere, preferably nitrogen, by heating under reflux.
• the product may be obtained by heating the reaction mixture to dryness, and purifying chromatographically on silica gel.
• Esters of the compounds of formula (I) may be 3',5'- diesters, or 3'-mono or 5'-mono esters, and these may be prepared by acylating the compounds of formula (I) with an appropriate acylating agent, such as organic acid chloride or anhydride, under normal acylating conditions.
• an appropriate acylating agent such as organic acid chloride or anhydride
• the compounds of formula (I) or esters thereof may be formulated for use in a pharmaceutical composition. Accordingly, in a further aspect of the invention, there is provided a pharmaceutical composition which comprises a compound of the formula (I) or ester thereof together with a pharmaceutically acceptable carrier or excipient.
• compositions which may be given by the oral route may be compounded in the form of syrups, tablets and capsules.
• any pharmaceutical carrier suitable for formulating such solid compositions may be used, for example magnesium stearate, starch, lactose, glucose, rice, flour and chalk.
• the composition may also be in the form of an ingestible capsule, for example of gelatin, to contain the compound, or in the form of a syrup, a solution or a suspension.
• Suitable liquid pharmaceutical carriers include ethyl alcohol, glycerine, saline and water to which flavouring or colouring agents may be added to form syrups.
• the compounds may also be presented with a sterile liquid carrier for injection.
• composition may also be formulated for topical application to the skin or eyes.
• the compounds of the invention may be made up into a cream, lotion or ointment.
• These formulations may be conventional formulations well known in the art, for example, as described in standard books of pharmaceutics and cosmetics, such as Harry's Cosmeticology published by Leonard Hill Books, and the British Pharmacopaeia.
• composition for application to the eyes may be a conventional eye-drop composition well known in the art.
• compositions of this invention are in unit dosage form or in some other form that the patient may administer to himself a single dose.
• a suitable dosage unit might contain from 50 mg to 1 g of active ingredient, for example 100 to 500 mg.
• Such doses may be adminstered 1 to 4 times a day or more usually 2 or 3 times a day.
• the effective dose of compound depends on the particular compound employed, but is in general in the range of from 1.0 mg/kg/day to 20 mg/kg of body weight per day or more usually 2.0 mg/kg/day to 10 mg/kg/day.
• a method of treating viral infections in human or non-human animals which comprises administering to the animal an effective amount of a compound of formula (I) or a pharmaceutically acceptable active ester thereof.
• Vero African Green Monkey Kidney cells were grown to confluence in 6 well multidishes, each well being 3.5 cm in diameter. The cells were incubated with Herpes simplex type 1 virus (HFEM strain) and overlaid with 0.5 ml of 0.9% agarose (w/v) in maintenance medium containing the test compound at a range of concentrations from 100 pg/mL in half-log dilution steps. The virus infected cultures were then incubated at 37°C for 6 days before fixing in 4% formaldehyde solution and staining with carbolfuchsin. The dishes were then examined to find what concentration of test compound causing a 50% reduction in the number of virus plaques formed (PDD 50 value) and the minimum concentration of test compound which killed the cell monolayer, leaving a clear zone devoid of cells and virus plaques (MTD).
• PDD 50 value concentration of test compound which killed the cell monolayer

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Engineering & Computer Science (AREA)
• Biochemistry (AREA)
• Biotechnology (AREA)
• General Health & Medical Sciences (AREA)
• Genetics & Genomics (AREA)
• Molecular Biology (AREA)
• Saccharide Compounds (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Applications Claiming Priority (2)

Publications (1)

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ID=10523631

Family Applications (1)

Country Status (5)

Cited By (2)

Citations (2)

• 1982
  • 1982-07-26 EP EP82303933A patent/EP0072137A1/de not_active Ceased
  • 1982-07-30 ES ES514597A patent/ES514597A0/es active Granted
  • 1982-07-30 AU AU86632/82A patent/AU8663282A/en not_active Abandoned
  • 1982-07-30 JP JP57133616A patent/JPS5826896A/ja active Pending
  • 1982-07-30 ZA ZA825525A patent/ZA825525B/xx unknown

Patent Citations (2)

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